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MicroRNAs (miRNAs) can regulate cell survival and death by targeting apoptosis-related gene expression. miR-210 is one of the most hypoxia-sensitive miRNAs. In this study, we evaluated the roles of miR-210 in hypoxia-induced insults to neural cells. Treatment of neuro-2a cells with oxygen/glucose deprivation (OGD) induced cell apoptosis in a time-dependent manner. In parallel, OGD time-dependently increased cellular miR-210 levels. Knocking down miR-210 expression using specific antisenses significantly attenuated OGD-induced neural apoptosis. Concurrently, OGD increased hypoxia-inducible factor (HIF)-1α mRNA and protein syntheses. Pretreatment with YC-1, an inhibitor of HIF-1α, reduced OGD-caused cell death. Sequentially, OGD specifically decreased antiapoptotic Bcl-2 mRNA and protein levels in neuro-2a cells. A search by a bioinformatic approach revealed that miR-210-specific binding elements exist in the 3'-untranslated region of Bcl-2 mRNA. Application of miR-210 antisenses simultaneously alleviated OGD-involved inhibition of Bcl-2 mRNA expression. In comparison, overexpression of miR-210 synergistically diminished OGD-caused inhibition of Bcl-2 mRNA expression and consequently induced greater cellular insults. Taken together, this study shows that OGD can induce miR-210 expression through activating HIF-1α. And miR-210 can mediate hypoxia-induced neural apoptosis by targeting Bcl-2.

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Nineteen compounds have been isolated from the methanol extract of the root and aerial parts of Ruta graveolens. The structural elucidation of these isolated compounds were determined by the spectroscopic methods and/or comparison of the physical data with literature values. Their antiplatelet aggregation and cytotoxic activities were examined to find potent antiplatelet aggregation and cytotoxic compounds from natural resources. Among them, dictamine (5), skimmianine (7), psoralen (8), chalepensin (12), clausindin (13), and graveolinine (16) showed significant inhibition of platelet aggregation, induced by arachidonic acid and collagen. Arborinine (2), dictamine (5), isopimpinellin (11), clausindin (13), and graveoline (17) exhibited cytotoxic activity against KB, Hela, DLD, NCI and Hepa tumor cell lines.

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